2型糖尿病モデル動物Goto-Kakizakiラットにおける11β-Hydroxysteroid Dehydrogenaseの変動〜肝臓における上昇および脂肪組織における低下〜

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By activating inert 11-dehydrocorticosterone,11β-Hydroxysteroid dehydrogenase(11β-HSDI)is strongly considered to play a pivotal role in the development of insulin resistance in diabetes mellitus in rodents.However,it still remain unknown whether 11β-HSDI activity fluctuates in the Goto-Kakizaki(GK) rat model of type 2 diabetes mellitus.Additionally,11β-HSDI has another important role in the reductive metabolism of xenobiotic carbonyl compounds.Here,we investigated 11β-HSDI activity as well as expression levels of protein and mRNA to understand the role of 11β-HSDI in development of type 2 diabetes and its effects on the pharmacokinetics of carbonyl compounds in GK rats.11β-HSDI activities towards endogenous corticosterone and synthetic prednisolone as well as xenobiotic metyrapone were significantly increased in the liver of GK rats compared to those of control rats.Elevated expresson levels of protein and mRNA were also observed.In contrast,those paraments were signficantry decreased in the adipose tissues of GK rats than in control rats.The results suggest that expression of 11β-HSDI is tissue-specific and increased hepatic 11β-HSDI activity might be related to the development of insulin resistance in GK rats. The elevation of hepatic 11β-HSDI activity might result in the rapid elimination of xenobiotic carbonyl compounds in GK rats.
東北薬科大学の論文